Neuroinflammation Question Bank

An 18-year-old Caucasian boy presents with skin lesions and recurrent fevers. 

On examination, he has aphthous ulcers, a right lower motor neurone facial palsy and multi-directional nystagmus with evidence of limb intention tremor and dysmetria. His GCS is 14/15 (M5V5E4). 

His MRI brain is shown below. A lumbar puncture is performed and a CSF reveals 45 white cells (100% lymphocytes), 2 red cells, protein 0.9g/L, glucose 4mmol/L (plasma 6mmol/L) and matched oligoclonal bands. 

What is the likely cause of his presentation?

A 74-year-old male presents to the emergency department with a 2-week history of episodic memory impairment and seizures. His past medical history includes alcohol excess and new depression. On arrival, you review his notes and discover the seizure semiology includes hemifacial movement and arm jerking. 

Examination is non-localising but his GCS is 12/15 (M5V4E3). His MRI is shown below. An EEG shows general slowing and CSF reveal a moderate lymphocytic pleocytosis. 

What is the likely cause for his presentation?

A 46-year-old male presented to hospital with a depressed level of consciousness. His past medical history includes familial hypercholesterolaemia, vertigo and testicular cancer. He drinks alcohol most days. On discussion with his wife she has noted him complaining of unsteadiness over the past couple of weeks with tinnitus, hearing loss and memory concerns. 

On examination, his GCS is 10 (M5V3E3) and his observations are stable. There is vertical skew and a painful stimulus evokes an uncoordinated limb localisation. His plantars are extensor and reflexes brisk. 

An MRI reveals a rhombencephalitis. 

His LP reveals a moderate lymphocytic pleocytosis with gram stain and culture pending. 

What is the likely cause?

The anti-JC virus antibody titres of a 34-year-old female with relapsing-remitting multiple sclerosis, maintained on Tysabri for 2 years, have been reported elevated. She has rapidly evolving multiple sclerosis, with a current EDSS of 4.0 and has not been exposed to any previous disease modifying therapies. She has two children and is not considering further children. She is on adequate contraception in the form of a long-acting reversible contraceptive. 

You discuss the risk of PML and both agree on a medication switch, opting for a management strategy that minimises the chance of irreversible carry-over PML through a bridging therapy. 

Which bridging therapy would you offer from the following?

A 32-year-old Caucasian female presents with left-sided retro-orbital pain and blurred vision. Her symptoms have progressed over the course of 3 days to the point that it is affecting her work. She describes deteriorating central vision in the left eye with “washed out” colours. 

On examination, there is a left relative afferent pupillary defect, normal fundus, visual acuity of 20/100 and desaturation of red colour vision on the left. 

An MRI reveals evidence of demyelination. 

Which of the following is correct?

What is the broad risk of relapse in the next two years in a patient diagnosed with a clinically isolated syndrome if the presenting MRI-brain reveals any typical demyelinating lesion present?

What is the approximate risk of patients developing progressive multi-focal leukoencephalopathy (PML) if they are treated with natalizumab?

A 28-year-old female presents to the Emergency Department after a passer-by found her wandering the streets confused. She appears to be clutching her head and reports some pain. She is disorientated and is exhibiting some paranoid ideations and delusions.  You are unable to find any identification and she cannot articulate a clear past medical history. 

During your examination, she appears to respond minimally to auditory stimuli and Weber’s lateralises to the left with air conduction>bone conduction on both sides. Her limb examination reveals some mild limb ataxia bilaterally and fundoscopy shows evidence of a possible branch retinal artery occlusion. 

An MRI reveals demyelinating lesions with predilection for the corpus callosum and grey matter described as ‘snowballs’ in the report. CSF reveals a mild lymphocytic pleocytosis (10 cells/mm³) and protein is 1g/L with normal glucose and lactate, negative viral PCR and no oligoclonal bands. 

What is the likely diagnosis?

A 34-year-old female is seen in outpatient neurology follow-up accompanied by her husband. She was admitted 6 weeks ago with headaches and fevers and had been started on treatment for confirmed herpes simplex virus 1 encephalitis (HSVE). She made a good recovery 3 weeks following her illness onset and was discharged with early follow-up. Upon questioning, her husband reports a progressive decline in her mood and memory over the past week and you note the patient is exhibiting agitation and delusions during the consultation. She is re-admitted for further investigations and to re-commence IV aciclovir. 

A lumbar puncture is performed and reveals a protein of 0.61g/dL, mild lymphocytic pleocytosis (17 per mm³) and negative HSV-1 PCR. 

What is the most likely investigation to yield the correct diagnosis?

A 72-year-old woman is admitted with headache and confusion on a background of mild cognitive decline in the preceding 12 months. Her husband reports she has become acutely confused since her headache began. She had been previously well and took no regular medication. 

On examination, she lacked insight into her condition and was indifferent to food and drink. There was a right homonymous hemianopia with evidence of additional Gerstmann syndrome. 

An MRI-brain revealed a diffuse leukodystophy (L>R) with diffuse meningeal and patchy gyral cortical gadolinium enhancement with no evidence of an acute stroke. An extensive investigatory work-up revealed evidence of a CSF lymphocytic pleocytosis (12 per mm3) but autoantibodies and RT-QuIC were normal. Digital subtraction angiography revealed evidence of beading and stenosis. Given the diagnostic uncertainty, a brain biopsy was performed, which revealed widespread concentric eosinophilic wall thickening of the leptomeningeal and cortical blood vessels, surrounded by lympho-histiocytic inflammation with positive immunostaining for amyloid-β. 

What is the diagnosis?

A 28-year-old female attends neurology outpatients’ clinic following an episode of blurred vision in her left eye and colours appear washed out. Six months previously she reported tingling in her arms lasting two weeks following the birth of her child. 12 months previously she experienced a severe bout of vertigo lasting 10 days. 

Her past medical history includes migraines for which she is taking propranolol.

Your examination confirms a left optic neuritis and an MRI-brain scan reveals 9 demyelinating plaques with one lesion enhancing following administration of contrast.

She would like to conceive in the next year or two. Which of the following disease modifying treatment would be most appropriate?

A 10-year-old boy presents with progressive visual impairment and cognitive decline. On examination, he has spasticity and hyperreflexia. An MRI-brain is shown in the figure below. 

Genetic testing is most likely to reveal a mutation in which of the following genes?

A 28-year-old male with a 2-year history of relapsing-remitting multiple sclerosis presents with symptoms compatible with optic neuritis. His estimated EDSS is 2.5.  He receives a course of oral methylprednisolone with omeprazole cover. 

One week later, he returns with left groin pain and hip flexor weakness. His vitals are stable and other systems examinations are satisfactory.

How should this be managed?

Which of the following autoantibody syndromes may cause a clinical presentation of diarrhoea, myoclonus, hyperekplexia, encephalopathy and weight loss?

A 23-year-old male presents to the emergency department with a one-week history of fever with later progressive confusion. 

Neurological examination reveals weakness of the right arm and leg. There is no RAPD and the patient has normal optic discs. 

A lumbar puncture reveals elevated protein and a mild pleocytosis without the presence of oligoclonal bands. No organisms are cultured and viral PCR is negative. MRI of the brain is shown below.

What is the most likely diagnosis in this patient?

Which of the following can cause isolated bithalamic orbitostriatal lesions?

A 32-year-old female presents with subacute encephalopathy and seizures leading to new-onset refractory status epilepticus. Her MRI brain is normal and lumbar puncture reveals a moderate lymphocytic pleocytosis with cultures pending. An EEG is shown below.

What is the likely test to confirm the probable diagnosis?

A 30-year-old woman attends the MS clinic. She was diagnosed with relapsing remitting MS 6 years previously. She was treated with interferon beta (Avonex) until age 28, when 2 relapses in 12 months prompted her neurologist to escalate her treatment to cladribine. During your consultation she discloses no relapses over the last 4 months, when she received the first dose of cladribine. 

Her EDSS is 2.0 (visual acuity on the left 6/7.5, mild left-sided weakness) following her last relapse, which affected multiple areas of the neuroaxis and necessitated hospital admission for IV methylprednisolone and a prolonged period of rehabilitation. She and her partner are trying to conceive.

What is the most appropriate management?

A 27-year-old Afro-Caribbean lady attends the emergency Neurology clinic with a 3-day history of ascending bilateral sensory disturbance affecting both legs and a 24-hour history of bilateral leg weakness and difficulty passing urine. 

She has a history of systemic lupus erythematosus, diagnosed 3 years ago when investigation for bilateral small joint arthritis and a malar rash revealed elevated ANA and antibodies to dsDNA and cardiolipin. She has been asymptomatic on hydroxychloroquine 100mg BD. She also has Coeliac disease with anti-TTG antibodies. 

A month prior to attendance she reports an episode of food poisoning with 2 weeks of constant vomiting and weight loss. Her mother also has SLE. Her father died of a stroke at age 62.

She takes hydroxychloroquine 100mg BD and aspirin 75mg OD. 

She has not travelled abroad recently and does not smoke or use recreational drugs. 

An MRI scan of her spinal cord revels a longitudinally extensive transverse myelitis.

What is the most likely diagnosis?

A 26-year-old woman is referred to the Neurology clinic by her Ophthalmology consultant. Three months prior she had been diagnosed with unilateral optic neuritis. She denies any neurological symptoms before or since the event.

On examination, visual acuity is 6/4 on the right and 6/7.5 on the left, with a left RAPD and pallor of the left optic disc. The remainder of the examination is normal. 

You organise further investigations. A lumbar puncture reveals acellular CSF with unpaired oligoclonal bands. An MRI brain and spinal cord shows two inflammatory-appearing T2 hyperintensities in the left frontal white matter with no enhancement after gadolinium.

What is the correct diagnosis?

The risk of converting from clinically isolated syndrome to MS (i.e., experiencing a relapse) is determined by 4 of the following. 

Which of these options is NOT predictive of conversion to MS?

The following screening tests and vaccination schedules are mandatory for which of the disease modifying therapies listed?

• Interferon gamma release assay for TB
• Varicella zoster antibody titres (vaccination if seronegative)
• Hepatitis B and C screening
• HIV screening
• Avoidance of live vaccines for 4-6 weeks prior to commencing treatment until white cell values in normal ranges

You are called to review a 40-year-old man on the Haematology ward. He was diagnosed with mantle cell lymphoma a year ago. Although it responded initially to a tyrosine kinase inhibitor, he had a radiological relapse 2 months ago and the decision was made to escalate to Chimeric Antigen Receptor T-cell (CAR-T-cell therapy). He received the cell infusion 7 days prior to your review.

The SHO explains they are concerned the patient has developed Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and would like your opinion. 

On examination, the patient is sleepy but responsive to voice. There is no focal neurological deficit and optic discs appear normal. 

His respiratory and cardiac observations are all within the normal ranges. Blood glucose is 5.1 mmol/L and he is apyrexial. CRP and interleukin-6 levels are checked daily and are normal.

You request an MRI and EEG. MRI brain is unremarkable. EEG shows diffuse slowing without epileptiform features.

What is your management?

A 46-year-old male presents with unsteadiness and seizures. He has a medical history of hypertension, autoimmune hypothyroidism, undifferentiated bone pain, hypercholesterolaemia and is being investigated for polydipsia and polyuria.

On examination you note bilateral (R>L) intention tremors with dysmetria and poor heel-shin co-ordination. There is also some subtle right-sided weakness – MRC 3/5 – in a pyramidal distribution. A MOCA is performed due to some subtle cognitive impairment noted subjectively, which reveals poor verbal fluency, executive function and memory. 

An MRI-brain reveals an ill-defined tumour-like lesion around the pons and cerebellar peduncles with concomitant cerebellar atrophy. 

A discussion with the neurosurgeons occurs and the decision to undergo a biopsy of the lesion is suggested. Neuropathology of the tissue reveals lipid-laden macrophages which stain positive for CD68, negative for CD1a and S100, with gliosis and Touton giant cell formation. Cells also stain for CD163 with surrounding demyelination. Molecular analysis reveals BRAF V600E variant.

What is the diagnosis?

A 54-year-old female is admitted to the Emergency Department with fever, headache and confusion. 

On examination, her temperature is 38.2, heart rate 78bpm, blood pressure 132/84mmHg, respiratory rate 14/minute and oxygen saturations 98% on room air. Neurological examination reveals a right relative afferent pupillary defect, bilateral intention tremors and dysmetria but normal limb tone, reflexes and sensation. 

An MRI-brain is shown below. Cerebrospinal fluid reveals 80/mm³ white cells (80% lymphocytes), 2/mm³ red cells, protein 1.2g/L. Viral PCR is pending. Initial microscopy, culture and sensitivity is negative. Acid fast bacilli has returned negative. CT chest abdomen and pelvis in unremarkable.

Which of the following tests will help clarify the diagnosis?

A 3-month-old boy is noted by his parents to be floppy and have ‘abnormal eye movements’. His parents specifically report poor head control and he is yet to smile. 

On examination, there is multi-directional nystagmus in multiple eccentric gazes, hypotonia, global ataxia and head tremor. 

An MRI brain is performed and shown below.

A genetic leukodytrophy panel is subsequently sent which reveals a mutation in the PLP1 gene. 

What is the diagnosis?

A 42-year-old female presents to the Outpatient Department with cognitive impairment and trouble mobilising. She is accompanied by her husband who informs you that her symptoms have been progressed over the course of a year or so but she has been reluctant to seek help. She has no significant past medical history. There is a family history of early dementia, psychiatric changes and balance problems in the mother and maternal aunt and grandfather; although their diagnosis is unclear. 

On examination, she is stooped with a broad-based gait and reduced arm swing. There is evidence of spasticity in the limbs and also bradykinesia. Her power is sufficient and her reflexes are globally brisk with extensor plantars bilaterally. Sensation in satisfactory in all modalities. There is evidence of bilateral heel-shin ataxia and upper limb dysmetria and intention tremors. Her Montreal Cognitive Assessment is 21/30 with deficits in executive function, verbal memory and recall. 

She is commenced on levodopa and an MRI-brain is requested (shown below).

She returns 2-months later with no improvement following levodopa. 

Genetics are sent which returns a missense mutation in the CSF1R gene.

What is the diagnosis?

A 30-year-old male presents to the Outpatients Department with memory problems and personality changes over the past 4 months. His wife found him wandering in familiar places and noted he forgot to pay the bills for two months running. In the Outpatient Department, he was aggressive and combative requiring admission to the ward where he later calmed down for a formal examination and investigation work-up. 

On examination, his GCS is 14/15 (M5 V5 E4). There is no focal neurological deficit. He is cachectic and you note supraclavicular and axillary lymphadenopathy. His Montreal Cognitive Assessment (MoCA) is 16/30. 

An MRI-brain reveals hyperintensities of the medial temporal lobes. A CSF examination reveals a lymphocytic pleocytosis (50 white cells/mm³), protein 0.9g/L and cytology/flow cytometry negative.  A CT-chest/abdomen/pelvis reveals widespread lymphadenopathy with a later supraclavicular lymph node biopsy revealing nodular sclerosing Hodgkin’s lymphoma.

Which of the following blood test would help secure the full diagnosis explaining his presentation?

A 9-year-old girl is seen in the Outpatients Department with progressive cognitive decline and balance issues. Her mother has noted a slow deterioration in her studies compared to her baseline. She has always required special-needs education. Of note, when she suffers from a cold or other viral-related illness her studies suffer more for a few weeks following recovery. In addition she suffers from poor balance on ambulation which has progressed over the past two years. Her past medical history includes delayed puberty, myopia and hypodontia.

On examination you note a short stature and gait ataxia. Limb examination reveal no motor or sensory deficit but significant intention tremor and dysmetria bilaterally. Her reflexes are brisk on both sides but her plantars went down. Her Montreal Cognitive Assessment was 26/30 with marks primarily deducted in executive function.

An MRI-brain is organised which revealed areas of hypomyelination with myelination present in the optic radiation. Moreover, a small T2 hypointense dot was observed in the posterior limb of the internal capsules and T2 hypointensities also seen in the venterolateral thalamus and dentate nucleus. There is also cerebellar atrophy and thinning of the corpus callosum.

In view of the imaging findings, a genetic leukodystrophy screen was sent which returned a heterozygous mutation in the POLR3B gene.

What is the unifying diagnosis?

Which of the following neuroglial surface antibodies are associated with a combination of sleep disorders (including REM/non-REM parasomnias, obstructive sleep apnoea or nocturnal stridor), bulbar dysfunction, vocal cord paralysis PSP-like disorder, dysautonomia and gait instability?